Macrophage Inhibitory Cytokine-1 (MIC-1) was first described in 1997 (Bootcov et al, Proc. Natl. Acad. Sci. October 1997) based on experiments showing increased expression in activated macrophages. MIC-1 has subsequently been identified by others and given several additional names such as placental transforming growth factor beta (PTGF-β), placental bone morphogenetic protein, growth differentiation factor-15 (GDF15), prostate derived factor (PDF), non-steroidal anti-inflammatory drug-activated gene (NAG-1) and PL74. MIC-1 is a distant member of the TGF-beta super family, a family of peptide hormones involved in cell growth and differentiation. MIC-1 circulates as a cysteine-rich homodimer with a molecular mass of 24.5 kDa. Human wild-type MIC-1 has a short half-life, meaning that treatment with wt-MIC-1 requires daily administration to maintain efficacy.
Accumulating evidence support the therapeutic utility of MIC-1 in metabolic disorders such as obesity and diabetes. Data from patients with advanced cancer showed that weight loss correlated with circulating levels of MIC-1 (Johnen et al, Nat Med., November, 2007). Transgenic mice overexpressing MIC-1 gain less weight and body fat both on a normal low fat diet and on a high fat diet (Macia et al, PLoS One, April, 2012). Also, transgenic mice overexpressing MIC-1 fed both on a low and high fat diet, respectively, had improved glucose tolerance compared with wild type animals on a comparable diet.
WO 2005099746 concerns a method of modulating appetite and/or body weight by administering a MIC-1 modulating agent.